Over the past 30 years, a wealth of information has been generated concerning the in vivo and in vitro properties of brain tumors and rodent models of brain tumor. The 9L gliosarcoma, which was generated from inbred Fisher rats, is a widely used syngeneic rat model for brain tumors. Originally produced by N-methyl-nitrosourea mutagenesis in Fisher rats, the tumor was cloned and designated 9L gliosarcoma because of its dual appearance of a glioblastoma and a sarcoma (Benda et al., J. Neurosurg., 34:310-323, 1971; Schmidek et al., J. Neurosurg., 34:335-340, 1971). The tumor could be proliferated under in vivo and in vitro conditions, making it a useful candidate as a glioma tumor model. The 9L gliosarcoma model clinically mimics rapidly growing and fatal intracerebral tumors, making it the most widely used rat brain tumor model.
Stem cells have been defined as multipotent, self-renewing cells with the potential to differentiate into multiple cell types. Systems have been developed to identify the first neural stem cells in a defined media, whereby striatal embryonic progenitors could be harvested and grown in culture as undifferentiated neurospheres (clonally derived aggregates of cells derived from a single stem cell) under the influence of the mitogens EGF and bFGF. Many of these cells expressed nestin (an intermediate filament found in neuroepithelial stem cells), but not markers for the more differentiated principal cell types of the CNS—neuronal and glial cells. However, when grown on coverslips treated with poly-L-ornithine, a substrate that allows cellular adhesion, many of the cells within the neurospheres differentiated into neurons and astrocytes with discontinued nestin expression. The isolated striatal cells fulfilled the critical features expected from neural stem cells: an unlimited capacity for self-renewal and capacity to differentiate into the principal mature neural cells (Potten et al., Development, 110:1001-1020, 1990; Lee et al., Nat. Neurosci., 8:723-729, 2005; Maric et al., J. Neurosci., 23:240-251, 2003; Weissman et al., Annu. Rev. Cell. Dev. Biol., 17:387-403, 2001; Seaberg et al., Trends Neurosci., 26:125-131, 2003; Reya et al., Nature, 414:105-111, 2001). Under similar circumstances “cancer stem cells” appear to have the same characteristics of self-renewal and multipotentcy.
Malignant brain tumors carry a poor prognosis even in the midst of surgical, radio-, and chemotherapy. With the poor prognosis of brain tumors amidst the available therapeutic treatments, there exists a significant need for more effective therapies to treat such tumors.